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Journal of Perianesthesia Nursing :... Jun 2024Hemoglobin M (Hb M) is a group of abnormal Hb variants that form methemoglobin, which leads to cyanosis. Patients with Hb M appear cyanotic but are usually asymptomatic....
Hemoglobin M (Hb M) is a group of abnormal Hb variants that form methemoglobin, which leads to cyanosis. Patients with Hb M appear cyanotic but are usually asymptomatic. Cyanosis with low peripheral oxygen saturation is unresponsive to oxygen therapy despite normal partial pressure of oxygen. As such, close attention should be paid during anesthesia. We report the first case of a Hb M patient undergoing laparoscopic uterine myomectomy under general anesthesia.
Topics: Humans; Female; Laparoscopy; Uterine Myomectomy; Adult; Uterine Neoplasms; Methemoglobinemia; Anesthesia, General; Leiomyoma
PubMed: 38159101
DOI: 10.1016/j.jopan.2023.08.025 -
Medicine Apr 2023Congenital methemoglobinemia is a rare cyanosis cause that can be manifested in affected individuals. We report a case of congenital methemoglobinemia after middle ear...
RATIONALE
Congenital methemoglobinemia is a rare cyanosis cause that can be manifested in affected individuals. We report a case of congenital methemoglobinemia after middle ear cholesteatoma resection under general anesthesia.
PATIENT CONCERNS
The primary concern of the patient is to safely perform cholesteatoma resection of the middle ear to reduce the pain associated with years of surgery and to survive the perioperative period.
DIAGNOSES
Congenital methemoglobinemia type 1.
INTERVENTIONS
The patient underwent general anesthesia and cholesteatoma resection of the middle ear.
OUTCOMES
The patient successfully underwent cholesteatoma resection in the middle ear under general anesthesia and went through the perioperative period smoothly, and successfully returned to society.
LESSONS
For patients requiring general anesthesia complicated with rare methemoglobinemia, we improve the awareness of crisis and make comprehensive preparation and monitoring, learn the pathophysiological mechanism related to the disease, so as to protect the operation of methemoglobin patients under general anesthesia.
Topics: Humans; Methemoglobinemia; Cholesteatoma, Middle Ear; Anesthesia, General; Ear, Middle; Cholesteatoma
PubMed: 37058021
DOI: 10.1097/MD.0000000000033561 -
Medicina (Kaunas, Lithuania) Mar 2023: Cardiopulmonary disorders are the most common cause of central cyanosis, and methemoglobinemia is often overlooked in the differential diagnosis of patients with...
: Cardiopulmonary disorders are the most common cause of central cyanosis, and methemoglobinemia is often overlooked in the differential diagnosis of patients with central cyanosis. In most cases, methemoglobinemia is acquired and hereditary congenital methemoglobinemia is rare. Only a few case reports of congenital methemoglobinemia can be found in PubMed. To date, only four cases of congenital methemoglobinemia diagnosed after the age of 50 years have been reported. : A 79-year-old Japanese woman presented at our hospital with the chief complaints of dyspnea and cyanosis. She exhibited cyanosis of the lips and extremities, and her SpO was 80%, with oxygen administration at 5 L/min. Blood gas analysis revealed a PaO of 325.4 mmHg and methemoglobin level of 36.9%. The SpO and PaO values were dissociated, and methemoglobin levels were markedly elevated. Genetic analysis revealed a nonsynonymous variant in the gene encoding nicotinamide adenine dinucleotide cytochrome (NADH) B5 reductase 3 (), and the patient was diagnosed with congenital methemoglobinemia. : It is important to consider methemoglobinemia in the differential diagnosis of patients with central cyanosis. At 79 years of age, our patient represents the oldest patient with this diagnosis. This report indicates that it is crucial to consider the possibility of methemoglobinemia regardless of the patient's age.
Topics: Humans; Female; Aged; Middle Aged; Methemoglobinemia; Methemoglobin; Cytochrome-B(5) Reductase; Cyanosis
PubMed: 36984616
DOI: 10.3390/medicina59030615 -
Medicina (Kaunas, Lithuania) Feb 2023: Mutations in the gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM...
: Mutations in the gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM exists as RCM type I (RCM1) and RCM type II (RCM2). RCM1 leads to higher methemoglobin levels causing only cyanosis, while in RCM2, neurological complications are also present along with cyanosis. : In the current study, a consanguineous Pakistani family with three individuals showing clinical manifestations of cyanosis, chest pain radiating to the left arm, dyspnea, orthopnea, and hemoptysis was studied. Following clinical assessment, a search for the causative gene was performed using whole exome sequencing (WES) and Sanger sequencing. Various variant effect prediction tools and ACMG criteria were applied to interpret the pathogenicity of the prioritized variants. Molecular dynamic simulation studies of wild and mutant systems were performed to determine the stability of the mutant CYB5R3 protein. : Data analysis of WES revealed a novel homozygous missense variant NM_001171660.2: c.670A > T: NP_001165131.1: p.(Ile224Phe) in exon 8 of the gene located on chromosome 22q13.2. Sanger sequencing validated the segregation of the identified variant with the disease phenotype within the family. Bioinformatics prediction tools and ACMG guidelines predicted the identified variant p.(Ile224Phe) as disease-causing and likely pathogenic, respectively. Molecular dynamics study revealed that the variant p.(Ile224Phe) in the CYB5R3 resides in the NADH domain of the protein, the aberrant function of which is detrimental. : The present study expanded the variant spectrum of the gene. This will facilitate genetic counselling of the same and other similar families carrying mutations in the gene.
Topics: Humans; Methemoglobinemia; Molecular Dynamics Simulation; NAD; Mutation; Cyanosis; Cytochrome-B(5) Reductase
PubMed: 36837579
DOI: 10.3390/medicina59020379 -
American Journal of Veterinary Research Jan 2023To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry...
Inflammatory phenotype, clinicopathologic variables, and effects of long-term methylene blue in dogs with hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency.
OBJECTIVE
To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry results, and describe changes in methemoglobin (MetHb) levels and serum C-reactive protein (CRP) concentrations after long-term per os (PO) methylene blue (MB) therapy.
ANIMALS
21 client-owned dogs (CYB5R deficient, n = 10; healthy controls, 11).
PROCEDURES
In this prospective, case-control study, methemoglobin levels were measured using a blood gas analyzer with co-oximetry. Plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were measured using a canine-specific multiplex bead-based assay. Serum CRP concentrations were measured with a canine-specific commercial ELISA kit. Serum CRP concentration and MetHb levels were measured in 6 dogs with CYB5R deficiency after ≥ 60 days of PO MB therapy.
RESULTS
As expected, MetHb levels were higher in dogs with CYB5R deficiency compared to controls (P < .001). Plasma TNF-α, IL-6, IL-10, and serum CRP concentrations were no different between CYB5R-deficient and control dogs. Dogs with CYB5R deficiency had lower absolute lymphocyte (P = .005) and eosinophil counts (P = .04) and higher alanine transaminase (P = .04) and alkaline phosphatase activity (P = .02) than controls, but these changes were not clinically relevant. Methemoglobin levels decreased after PO MB therapy (P = .03).
CLINICAL RELEVANCE
These results suggest that otherwise healthy dogs with CYB5R deficiency do not have a constitutive proinflammatory phenotype and clinically relevant abnormalities in hematologic and serum chemistry panels are not expected. Dogs with decreased quality of life attributed to methemoglobinemia from CYB5R deficiency might benefit from PO MB therapy.
Topics: Dogs; Animals; Methemoglobinemia; Methylene Blue; Methemoglobin; Interleukin-10; Cytochromes b5; Interleukin-6; Tumor Necrosis Factor-alpha; Case-Control Studies; Prospective Studies; Quality of Life; Cytochrome-B(5) Reductase; Phenotype; Dog Diseases
PubMed: 36638001
DOI: 10.2460/ajvr.22.09.0155 -
Maternal Health, Neonatology and... Sep 2022Methemoglobinemia can be an acquired or congenital condition. The acquired form occurs from exposure to oxidative agents. Congenital methemoglobinemia is a rare and...
BACKGROUND
Methemoglobinemia can be an acquired or congenital condition. The acquired form occurs from exposure to oxidative agents. Congenital methemoglobinemia is a rare and potentially life-threatening cause of cyanosis in newborns that can be caused by either cytochrome B reductase or hemoglobin variants known as Hemoglobin M.
CASE PRESENTATION
A term male infant developed cyanosis and hypoxia shortly after birth after an uncomplicated pregnancy, with oxygen saturations persistently 70-80% despite 1.0 FiO2 and respiratory support of CPAP+ 6 cm H2O. Pre- and post-ductal saturations were equal and remained below 85%. Initial radiographic and echography imaging was normal. Capillary blood gas values were reassuring with normal pH and an elevated pO2. Investigations to rule out hemolysis and end-organ dysfunction were within acceptable range. Given the absence of clear cardiac or pulmonary etiology of persistent cyanosis, hematologic causes such as methemoglobinemia were explored. No family history was available at the time of transfer to our institution. Unconjugated hyperbilirubinemia > 5 mg/dL (442 μmol/L) interfered with laboratory equipment measurement, making accurate methemoglobin levels unattainable despite multiple attempts. Initial treatment with methylene blue or ascorbic acid was considered. However, upon arrival of the presumed biological father, a thorough history revealed an extensive paternal family history of neonatal cyanosis due to a rare mutation resulting in a hemoglobin M variant. Given this new information, hematology recommended supportive care as well as further testing to confirm the diagnosis of congenital methemoglobinopathy. Whole genome sequencing revealed a likely pathogenic variation in hemoglobin. The neonate was discharged home at 2 weeks of age on full oral feeds with 0.25 L/min nasal cannula as respiratory support, with close outpatient follow-up. By 5 weeks of age, he was weaned off respiratory support.
CONCLUSION
Congenital methemoglobinemia should be considered in the differential diagnosis for newborns with persistent hypoxemia despite normal imaging and laboratory values. Accurate quantification of methemoglobin concentrations is challenging in neonates due to the presence of other substances that absorb light at similar wavelengths, including HbF, bilirubin, and lipids.
PubMed: 36114590
DOI: 10.1186/s40748-022-00142-0 -
Journal of Investigative Medicine High... 2022Methemoglobinemia is a rare cause of hypoxia and can be a diagnostic challenge early in the disease course. The incidence of medication-induced methemoglobinemia is more...
Methemoglobinemia is a rare cause of hypoxia and can be a diagnostic challenge early in the disease course. The incidence of medication-induced methemoglobinemia is more common than congenital-related methemoglobinemia. The most common cause of methemoglobinemia is exposure to household detergents, illicit drugs, or medications with nitrate or sulfonamide chemical groups. The 2 main medications accounting for up to 45% of medication-induced cases are dapsone and benzocaine. We report a case of hypoxia and diarrhea with an arterial blood gas (ABG) showing methemoglobinemia at 26%. Infectious and autoimmune workup were negative. Methemoglobinemia level returned to normal level within 2 weeks of hydrochlorothiazide discontinuation, suggesting medication-induced methemoglobinemia at appropriate hypertension dosage. In this case, there was an acute rise in methemoglobin levels following initiation of an hydrochlorothiazide-losartan combination, which improved following the discontinuation of hydrochlorothiazide. Extensive workup ruled out cytochrome b5 reductase (Cb5R) and Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which raised the suspicion of hydrochlorothiazide-induced methemoglobinemia, as it is part of the sulfa drug family.
Topics: Hemoglobin M; Humans; Hydrochlorothiazide; Hypoxia; Methemoglobinemia
PubMed: 35959982
DOI: 10.1177/23247096221117919 -
JPMA. the Journal of the Pakistan... Jun 2022Haemoglobin contains iron in a ferrous form. When the iron is oxidized, it is called Methaemoglobin (MetHb). MetHb leads to tissue hypoxia, cyanosis, and secondary...
Haemoglobin contains iron in a ferrous form. When the iron is oxidized, it is called Methaemoglobin (MetHb). MetHb leads to tissue hypoxia, cyanosis, and secondary polycythemia. Methaemoglobinaemia is acquired or congenital. In this case, a 22-years-old male patient presented with cyanosis, headache, and lack of concentration. Cyanosis was present since birth. His previous investigations showed polycythemia. He was misdiagnosed on multiple occasions and was undergoing venesections for polycythemia. On evaluation at a private clinic, an Oxygen saturation gap was noted between the results of the pulse oximeter and arterial blood gas analyzer. This raised suspicion on the presence of MetHb. He was referred to Armed Forces Institute of Pathology, Rawalpindi for further workup.The sample obtained for MetHb was chocolate brown in colour. Analysis was done via co-oximetry. A high level of MetHb (45.6%) was obtained. All other radiological and haematological investigations were in the normal range. On the basis of history, clinical presentation, and investigations, he was diagnosed as a case of congenital methaemoglobinaemia with secondary polycythemia.
Topics: Adult; Cyanosis; Hemoglobin M; Humans; Iron; Male; Methemoglobinemia; Polycythemia; Young Adult
PubMed: 35751341
DOI: 10.47391/JPMA.2129 -
Biophysical Journal Jul 2022Hemoglobins M (Hbs M) are human hemoglobin variants in which either the α or β subunit contains a ferric heme in the αβ tetramer. Though the ferric subunit cannot...
Hemoglobins M (Hbs M) are human hemoglobin variants in which either the α or β subunit contains a ferric heme in the αβ tetramer. Though the ferric subunit cannot bind O, it regulates O affinity of its counterpart ferrous subunit. We have investigated resonance Raman spectra of two Hbs, M Iwate (α87His → tyrosine [Tyr]) and M Boston (α58His → Tyr), having tyrosine as a heme axial ligand at proximal and distal positions, respectively, that exhibit unassigned resonance Raman bands arising from ferric (not ferrous) hemes at 899 and 876 cm. Our quantum chemical calculations using density functional theory on Fe-porphyrin models with p-cresol and/or 4-methylimidazole showed that the unassigned bands correspond to the breathing-like modes of Fe-bound Tyr and are sensitive to the Fe-O-C(Tyr) angle. Based on the frequencies of the Raman bands, the Fe-O-C(Tyr) angles of Hbs M Iwate and M Boston were predicted to be 153.5° and 129.2°, respectively. Consistent with this prediction, x-ray crystallographic analysis showed that the Fe-O-C(Tyr) angles of Hbs M Iwate and M Boston in the T quaternary structure were 153.6° and 134.6°, respectively. It also showed a similar Fe-O bond length (1.96 and 1.97 Å) and different tilting angles.
Topics: Crystallography; Density Functional Theory; Heme; Hemoglobin M; Humans; Spectrum Analysis, Raman; Tyrosine; Vibration
PubMed: 35689380
DOI: 10.1016/j.bpj.2022.06.012 -
The Medical Journal of Malaysia Nov 2021Methaemoglobinaemia occurs when there is >1% methaemoglobin in erythrocytes. In an infant, they can present either congenitally or in an acquired form. We present a rare...
Methaemoglobinaemia occurs when there is >1% methaemoglobin in erythrocytes. In an infant, they can present either congenitally or in an acquired form. We present a rare case of methaemoglobinaemia presenting simultaneously in a mother and infant pair. The mother and infant were discharged well on Day-4 post-delivery with both mother and baby recording oxygen saturation levels of 100%. On Day-7, during a routine clinic visit, they were incidentally found to be centrally cyanosed. There were no other abnormalities. On investigation, the methaemoglobin levels were elevated in the infant (23.9%) and mother (14.3%). Treatment with ascorbic acid normalised mother's methaemoglobin levels; but baby's levels remained high until the administration of oral methylene blue. Both baby and mother remained well and pink at last follow-up at 2 years 8 months of age. This case illustrates difficulties in ascertaining the cause of methaemoglobinaemia. Postdelivery, the mother-neonate pair were pink, and their haemoglobin electrophoresis were normal, hence it was unlikely to be congenital methaemoglobinaemia. The team could not identify any triggering factors for acquired methaemoglobinaemia. There was also the uncertainty of the necessity to treat the baby. This is because treatment is not without harmful effects and despite the high methaemoglobin levels, the infant was otherwise well. Only a single published paper recommended that high methaemoglobin levels must be treated, and the recommendation was not supported by evidence. Lessons learnt from our case are that neonates with methaemoglobinaemia can be safely treated with oral methylene blue, but more research is needed on the benefitrisk profile of treatment.
Topics: Ascorbic Acid; Female; Hemoglobin M; Humans; Infant; Infant, Newborn; Male; Methemoglobinemia; Mothers
PubMed: 34806687
DOI: No ID Found